Fernandes Philana, O'Donovan Tracey R, McKenna Sharon L, Forde Patrick F
Cancer Research at UCC, Western Gateway Building, University College Cork, T12 XF62 Cork, Ireland.
Cancers (Basel). 2019 Aug 14;11(8):1177. doi: 10.3390/cancers11081177.
Pancreatic cancer represents a major challenge in oncology. Poor permeability of the pancreas and resistance to currently available therapies are impediments to improved patient survival. By transiently increasing cell membrane porosity and increasing drug uptake, Electrochemotherapy (ECT) has the potential to overcome these issues. In this study, we have evaluated the response of human and murine pancreatic cancer cells, in vitro, to electroporation in combination with Bleomycin, Cisplatin, or Oxaliplatin (ECT). The cytotoxic actions of all three drugs are potentiated when combined with electroporation in these cells. The biochemical and morphological changes post ECT are associated with immunogenic cell death that occurs with necroptosis rather than apoptosis. Moreover, ECT-induced cell death is rescued by Nec-1 suggesting that necroptosis may play a role in cell death mediated by cancer therapies.
胰腺癌是肿瘤学领域的一项重大挑战。胰腺的低通透性以及对现有疗法的耐药性是提高患者生存率的障碍。通过短暂增加细胞膜孔隙率并提高药物摄取量，电化学疗法（ECT）有潜力克服这些问题。在本研究中，我们评估了人源和鼠源胰腺癌细胞在体外对与博来霉素、顺铂或奥沙利铂联合使用的电穿孔（ECT）的反应。在这些细胞中，当这三种药物与电穿孔联合使用时，其细胞毒性作用均得到增强。ECT后的生化和形态学变化与由坏死性凋亡而非凋亡引起的免疫原性细胞死亡有关。此外，Nec-1可挽救ECT诱导的细胞死亡，这表明坏死性凋亡可能在癌症治疗介导的细胞死亡中起作用。
